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Biomedical subjects

S Lagakos

Publications and source records attributed to S Lagakos.

16 recordsLinked to original sources
PubMed2000

Evaluation of HIV-1 immunogen, an immunologic modifier, administered to patients infected with HIV having 300 to 549 x 10(6)/L CD4 cell counts: A randomized controlled trial.

CONTEXT: Despite enormous improvements achieved through the use of antiretroviral therapies (ARTs), the risk for eventual human immunodeficiency virus (HIV) disease progression remains high. Agents that enhance the immunologic mechanism for viral recognition might reduce disease progression. OBJECTIVE: To determine whether the addition of HIV-1 Immunogen would confer added clinical efficacy to that achievable by ARTs. DESIGN AND SETTING: Multicenter, double-blind, placebo-controlled, randomized trial beginning March 1996 and ending May 1999 conducted at 77 centers in the United States providing primary care or referral care for persons infected with HIV. PATIENTS: Adults infected with HIV who have baseline CD4 cell counts between 300 x 10(6)/L and 549 x 10(6)/L without prior acquired immunodeficiency syndrome-defining conditions receiving stable ART (or no therapy) were screened and 2527 were randomized. INTERVENTIONS: Ten units of HIV-1 Immunogen, derived from a Zairian HIV isolate, inactivated and formulated with incomplete Freund adjuvant, was administered intramuscularly every 12 weeks. The placebo was incomplete Freund adjuvant. Changes in ARTs were allowed. MAIN OUTCOME MEASURES: HIV progression-free survival; secondary end points included overall survival, changes in HIV RNA, CD4 cell counts, CD4 percentage, body weight, and immunogenicity. RESULTS: The overall event rate was 1.8 per 100 person-years of follow-up. Fifty-three subjects developed clinical progression in each treatment group (relative risk [RR], 0.97; 95% confidence interval [CI], 0.66-1.42; P =.89). There were 19 and 23 deaths in the placebo and HIV-1 Immunogen groups, respectively (RR, 0.81; 95% CI, 0.44-1. 48; P =.49). There were no statistically significant differences between the groups with respect to changes in HIV RNA (P =.59), CD4 percentage (P =.63), or body weight (P =.89). Subjects in the HIV-1 Immunogen group had an increase in average CD4 cell count of approximately 10 x 10(6)/L greater than the placebo group (P =.02). CONCLUSION: HIV-1 Immunogen with unrestricted ART failed to demonstrate an increase in HIV progression-free survival. JAMA. 2000;284:2193-2202.

AIDS Vaccines↗
PubMed1991

Effects of zidovudine therapy in minority and other subpopulations with early HIV infection.

UNLABELLED: OBJECTIVE--The purpose of this study was to determine whether the beneficial effects of zidovudine seen overall in two recently completed placebo-controlled clinical trials are also apparent in blacks, Hispanics, women, and intravenous drug users. DESIGN--Two double-blind placebo-controlled randomized clinical trials, protocols 016 and 019, conducted by the AIDS Clinical Trials Group. SETTING--University-based referral centers. PARTICIPANTS--Two thousand forty-eight persons with asymptomatic or mildly symptomatic human immunodeficiency virus infection were analyzed. Of these, 155 were black, 190 were Hispanic, 144 were women, and 221 were intravenous drug users. All randomized subjects were included in the analysis. INTERVENTION--Participants in the AIDS Clinical Trials Group protocol 016 were assigned to receive a placebo or a 1200-mg daily dose of zidovudine. Participants in the AIDS Clinical Trials Group protocol 019 were assigned to receive a placebo, a 500-mg daily dose of zidovudine, or a 1500-mg daily dose of zidovudine. MAIN OUTCOME MEASURE--Progression to AIDS. RESULTS--The rates of progression to AIDS in subjects receiving zidovudine were significantly lower than those in subjects receiving a placebo among blacks (P = .03), whites (relative risk [RR] = 2.3, 95% confidence interval [CI] = 1.5 to 3.6, P less than .0001), Hispanics (RR = 4.4, CI = 1.2 to 16.8, P = .02), non-Hispanics (RR = 2.3, CI = 1.5 to 3.6, P = .0002), men (RR = 2.5, CI = 1.6 to 3.8, P less than .0001), and non-intravenous drug users (RR = 2.5, CI = 1.6 to 4.0, P less than .0001). The rates of disease progression for subjects receiving zidovudine were not statistically different from those receiving placebo for women (RR = 3.3, CI = 0.3 to 36.3, P = .31) or for intravenous drug users (RR = 2.0, CI = 0.7 to 6.2, P = .21); however, in both instances the estimated RRs were similar to those for men and non-intravenous drug users. CONCLUSIONS: -Although the two studies used for this analysis were not specifically designed to assess the effects of zidovudine in each separate subpopulation, the data suggest that the beneficial effects of zidovudine reported for the entire study population also apply to the subpopulations of blacks, Hispanics, women, and intravenous drug users.

Acquired Immunodeficiency Syndrome↗
PubMed1990

On the consequences of model misspecification in logistic regression.

Logistic regression models are commonly used to study the association between a binary response variable and an exposure variable. Besides the exposure of interest, other covariates are frequently included in the fitted model in order to control for their effects on outcome. Unfortunately, misspecification of the main exposure variable and the other covariates is not uncommon, and this can adversely affect tests of the association between the exposure and response. We allow the term "misspecification" to cover a broad range of modeling errors including measurement errors, discretizing continuous explanatory variables, and completely excluding covariates from the model. This paper reviews some recent results on the consequences of model misspecification on the large sample properties of likelihood score tests of association between exposure and response.

Animals↗
PubMed1982

Phase III study of CCNU, cyclophosphamide, adriamycin, vincristine, and VP-16 in small-cell carcinoma of the lung.

A comparison of CTX + CCNU and CTX + CCNU + procarbazine as initial systemic treatment was made in 440 evaluable patients with small-cell carcinoma of the lung. The overall response rate for patients receiving the three-drug combination was 57% (11% CR) compared with 44% (9% CR) for the two-drug combination. Median survival times were similar, 27 (with procarbazine) and 29 weeks (without procarbazine). Nonresponders to the initial treatment received ADR, ADR + VCR, and ADR + VP-16 with overall response rates of 14% (2 of 14), 27% (9 of 33), and 30% (15 of 51), respectively. Median survivals for nonresponders, as measured from day 42, were 15 weeks (ADR), 21 weeks (ADR + VCR), and 22 weeks (ADR + VP-16). Responders to the initial treatment either continued on the initial therapy or received a non-cross-resistant combination chemotherapeutic regimen (ADR + VCR) alternating with the initial therapy. There is also the suggestion that responders who received the cycled therapy after day 42 survived significantly longer than responders who did not switch treatments until relapse, 38 vs. 29 weeks.

Aged↗
PubMed1982

Radiotherapy of regional epidermoid carcinoma of the lung: a study in fractionation.

This paper reports a prospective randomized multicenter trial of two fractionation schemes in the supervoltage radiotherapy of locally inoperable epidermoid lung cancer. This study was stimulated by the need to provide improved and more acceptable treatment methods for patients with this condition, the most common cell type of lung cancer. The majority of such patients are not suitable for resection because of metastasis or because of extensive local disease, even though exploratory thoracotomy may be performed. It was therefore considered important to identify preferred methods of irradiation in this situation which is found in a large proportion of patients with lung cancer.

Adult↗
PubMed1981

A case study of statistics in the regulatory process: the FD&C Red No. 40 experiments.

Unexpected findings in a mouse study in which the safety of FD&C No. 40 (Red 40) was examined led to additional experimentation and to new statistical analyses and models. The possibility of acceleration of tumors raised questions about an operational definition of acceleration and of appropriate statistical methods for assessing acceleration, especially in the face of data dredging. The evaluation of Red 40 was further complicated by cage and litter effects and the multigenerational design. In this report the investigations of these studies are reviewed and are used to illustrate how new scientific work can emerge through the regulatory process. A number of issues in animal experimentation that need to be examind are indicated.

Animals↗
PubMedDate not supplied

Efficacy and safety of adefovir dipivoxil with antiretroviral therapy: a randomized controlled trial.

CONTEXT: Adefovir dipivoxil is a nucleotide analog that has demonstrated effective antiretroviral activity against human immunodeficiency virus (HIV) with once-daily administration. OBJECTIVE: To determine if adefovir confers antiretroviral or immunologic benefit when added to stable antiretroviral therapy. DESIGN: Multicenter, 24-week, randomized, double-blind, placebo-controlled study. Enrollment was conducted from June 3, 1996, through May 6, 1997. SETTING: Thirty-three US HIV treatment centers. PARTICIPANTS: Of 1171 patients screened, 442 patients infected with HIV receiving stable antiretroviral therapy for at least 8 weeks with plasma HIV RNA greater than 2500 copies/mL and CD4+ cell count above 0.20 x 10(9)/L were randomized. INTERVENTION: Patients were randomized to receive either a single 120-mg/d dose of adefovir dipivoxil (n = 219) or an indistinguishable placebo (n = 223). All patients received L-carnitine, 500 mg/d. Open-label adefovir was offered after 24 weeks and was continued until the end of the study. MAIN OUTCOME MEASURES: Changes in HIV RNA from baseline, based on area under the curve and CD4+ cell levels, adverse events, and effect of baseline genotypic resistance on response to adefovir. RESULTS: Patients assigned to adefovir demonstrated a 0.4-log10 decline from baseline in HIV RNA compared with no change in the placebo group (P<.001), which continued through 48 weeks. CD4+ cell counts did not change. During the initial 24 weeks, elevated hepatic enzyme levels (P<.001), gastrointestinal tract complaints (P<.001), and weight loss (P<.001) were associated with use of adefovir. Between 24 weeks and 48 weeks elevations in serum creatinine occurred in 60% of patients, usually returning to baseline after discontinuation of adefovir. Patients with lamivudine or lamivudine and zidovudine resistance mutations demonstrated anti-HIV effects with adefovir (P< or =.01 vs placebo group). CONCLUSIONS: This study suggests that once-daily adefovir therapy reduces HIV RNA and is active against isolates resistant to lamivudine or lamivudine and zidovudine. Nephrotoxicity occurred when treatment extended beyond 24 weeks but was reversible.

Adenine↗
PubMedDate not supplied

HIV treatment strategies utilizing virologic and immunologic markers as criteria for changing treatments.

Currently available antiviral drugs used in the treatment of AIDS patients are effective for a limited time. Therapy consisting of different drugs given in sequence thus has the potential to yield the greatest possible benefit to patients, yet it is not known in what order the drugs should be administered, or for how long. Can patient-specific information, such as viral load or determination of mutation status, be used to make these decisions on a patient by patient basis? We propose a general model for the relationship between treatment, virologic or immunologic markers, and clinical disease progression that can provide answers to these questions. We develop guidelines for optimizing progression under several settings. Optimal survival is derived for full, partial, or no interim information.

Acquired Immunodeficiency Syndrome↗